Glutathione-depleting polymer delivering chlorin e6 for enhancing photodynamic therapy.

The therapeutic effect of photodynamic therapy (PDT) is highly dependent on the intracellular production of reactive oxygen species (ROS). However, the ROS generated by photosensitizers can be consumed by the highly concentrated glutathione (GSH) in tumor cells, severely impairing the therapeutic effect of PDT. Herein, we synthesized a GSH-scavenging copolymer to deliver photosensitizer chlorin e6 (Ce6). The pyridyl disulfide groups, which have faster reactivity with the thiol groups of GSH than other disulfide groups, were grafted onto a hydrophobic block to encapsulate the Ce6. Under NIR irradiation, the Ce6 generated ROS to kill tumor cells, and the pyridyl disulfide groups depleted the GSH to prevent ROS consumption, which synergistically enhanced the therapeutic effect of PDT. In vitro and in vivo experiments confirmed the combinatory antitumor effect of Ce6-induced ROS generation and the pyridyl disulfide group-induced GSH depletion. Therefore, the pyridyl disulfide group-grafted amphiphilic copolymer provides a more efficient strategy for enhancing PDT and has promising potential for clinical application.

MiR-27b promotes sheep skeletal muscle satellite cell proliferation by targeting myostatin gene.

To investigate the role of miR-27b in sheep skeletal muscle development, here we first cloned the sequence of sheep pre-miR-27b, then further investigated its expression pattern in sheep skeletal muscle in vivo, the relationship of miR-27b expression and sheep skeletal muscle satellite cell proliferation and differentiation in vitro, and then finally confirmed its target gene during this development process. MiR-27b sequence, especially its mature sequence, was conservative among different species. MiR-27b highly expressed in sheep skeletal muscle than other tissues. In skeletal muscle of Suffolk and Bashbay sheep, miR-27b was upregulated during foetal period and downregulated during postnatal period significantly (P<0.01), but it still kept a relatively higher expression level in skeletal muscle of postnatal Suffolk sheep than Bashbay. There is a potential target site of miR-27b on 3'-UTR of sheep myostatin (MSTN) mRNA, and the double luciferase reporter assay proved that miR-27b could successfully bind on this site. When sheep satellite cells were in the proliferation status, miR-27b was upregulated and MSTN was downregulated significantly (P<0.01). When miR-27b mimics was transfected into sheep satellite cells, the cell proliferation was promoted and the protein level of MSTN was significantly downregulated (P<0.01). Moreover, miR-27b regulated its target gene MSTN by translation repression at an early step, and followed by inducing mRNA degradation in sheep satellite cells. Based on these results, we confirm that miR-27b could promote sheep skeletal muscle satellite cell proliferation by targeting MSTN and suppressing its expression.